A large nationwide study concludes that a drug called etanercept dramatically slows or even stops the progress of rheumatoid arthritis (RA) at the earliest stages of the disease, helping nearly three-quarters of those taking it. Etanercept also shows fewer side effects than the current best medicine.
While the drug has been on the market for several years as a symptom-easing therapy for people with advanced rheumatoid arthritis, this study marks a new use for etanercept as an early treatment. The study compared etanercept with the standard therapy, a drug called methotrexate.
"Both methotrexate and etanercept slow or actually halt the progress of the disease, but etanercept is more effective for more patients and has a low incidence of side effects," says rheumatologist Joan Bathon, M.D. Bathon led the year-long multicenter trials comparing the effect of the two drugs on 632 patients in the earliest stages of RA.
"The major drawback at this point," she adds, "is that etanercept is expensive — some $12,000 per patient per year, as compared with methotrexate's $1,000 a year."
The research, funded by the makers of etanercept and reported this week in the New England Journal of Medicine, forms the basis for new Food and Drug Administration guidelines governing use of the drug for early treatment. Physicians may now prescribe it, not only for symptom relief, but to prevent joint damage in the first place.
Rheumatoid arthritis is marked by an immune system attack on joints — both on bone and on the cartilage that surrounds the bone — bringing permanent joint damage. It affects joints in the hands and feet as well as all large joints. More than 6 million people in this country, most of them women, suffer from the disease. Symptoms include joint stiffness and pain and great fatigue.
Methotrexate, an anti-cancer drug, brought a treatment advance about 15 years ago, Bathon says. "But methotrexate's side effects can be significant, and nearly 50 percent of the patients taking it aren't helped."
Etanercept is a genetically engineered "designer drug" that blocks the action of a hormone-like chemical called tumor necrosis factor (TNF). TNF triggers much of the joint inflammation that comes with the disease, says Bathon, and also prompts cascades of reactions that end in destruction of cartilage in joints, as well as in bone erosion.
In the trial, people suffering from RA for three years or less received a 12-month course of either methotrexate or etanercept. Researchers selected subjects at especially high risk for joint destruction.
Using criteria from the American College of Rheumatology, the scientists looked for a decrease in swollen, tender joints, a drop in the laboratory measures of inflammation, for the improved evaluation of the disease by both patient and physician and — most important — for hard evidence from X-rays, says Bathon.
In the X-ray evaluation, patients were scored on a standard scale that measures how much bone erodes and, indirectly, how much cartilage disappears. At the end of the study, the majority of patients on either drug had no increase in bone erosion, with the progress of the disease completely stopped in 72 percent of the etanercept patients and in 60 percent of the methotrexate group. Patients on either drug also had a minimal increase in cartilage destruction.
The incidence of side effects serious enough to make patients stop taking methotrexate was about double that of the etanercept group, says Bathon. "We followed these patients for two years and it appears that the good effects are holding," she says.
Bathon cautions that neither drug is a cure. "But now if you start someone on methotrexate and see that person doesn't do well, you have an alternative," she says. "Also, combining the drugs seems to have no ill effects." Because TNF is a major immune system player though, physicians must watch patients carefully for increased signs of infection, she explains.
The study was funded by the Immunex Corporation, which makes Enbrel, the trade name for etanercept.
Other researchers were Richard W. Martin, M.D., of Michigan State University, Roy Fleischmann, M.D., of the Metroplex Clinical Research Center, Dallas, John Tesser, M.D., of the Phoenix Center for Clinical Research, Michael Schiff, M.D., of the Denver Arthritis Clinic, Edward Keystone, M.D., of Mt. Sinai hospital, Toronto, Mark Genovese, M.D., of Stanford University, Mary Chester Wasko, M.D., of the University of Pittsburgh Medical Center, Larry Moreland, M.D., of the University of Alabama at Birmingham, Arthur Weaver, M.D.,the Arthritis Center for Nebraska at Lincoln, Joseph Markenson, M.D., at the Hospital for Special Surgery, New York, and Barbara Finck, M.D, of Immunex Corporation, Seattle.
Related Web sites: For the Arthritis Foundation's page on RA, click on to http://www.arthritis.org/Answers/DiseaseCenter/ra.asp Also see this site: http://content.health.msn.com/content/dmk/dmk_summary_account_1437
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Journal
New England Journal of Medicine